crossing96/oncoscreening huggingface dataset:
Ha-ras oncogene-induced Stat3 phosphorylation enhances oncogenicity of the cell.	The ras oncogene needs a second factor to induce transformation and tumorigenicity of the cell. In this study, we show that mouse fibroblast 7-4-Stat3C cells overexpressing both Ha-ras(val12) oncogene and active-form Stat3 (Stat3C) showed higher colony formation in soft agar and xenograft tumor growth in BALB/c mice. Further studies show that both serine-727 and tyrosine-705 of Stat3 were phosphorylated while Ha-ras was overexpressed. Interleukin-6 (IL-6)-induced phosphorylation of tyrosine-705 and serine-727, as well as DNA-binding and transcriptional activity of Stat3 were further enhanced by Ha-ras overexpression. In addition, overexpression of Stat3C in 7-4-Stat3C cells prevented the cells from morphological change and apoptosis triggered by the Ha-ras oncogene under serum-depleted conditions. We demonstrate that Ha-ras and Stat3 acting together synergistically induce Stat3 phosphorylation at serine-727 phosphorylation and cyclin D1 expression and further enhance transformation and tumorigenicity of the cell. Ha-ras-induced Stat3 phosphorylation at serine-727 plays a pivotal role in transcriptional activation of cyclin D1 and suppression of cell apoptosis. The effect of Ha-ras on Stat3 phosphorylation at serine-727 was also detected in human bladder (T24) and lung (H460) cancer cells. Stat3 phosphorylation at serine-727 is important in Ras-related tumorigenesis.	bladder
Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine.	OBJECTIVES: To identify a better set of DNA methylation markers to detect superficial, low grade cancer cell in urine sediment for improving cancer treatment, morbidity, and mortality. MATERIALS AND METHODS: Methylation-specific PCR (MSP) assay was used to detect promoter hypermethylation in 4 genes (E-cadherin, p16, p14, and RASSF1A) to identify reliable biomarkers for bladder cancer diagnosis in primary tumor DNA and urine sediment DNA from 57 bladder cancer patients. Urine DNA was compared with 20 healthy controls. RESULTS: Fifty-one (90%) tumor DNA and 47 urine DNA (83%) samples from bladder cancer patients revealed hypermethylation in at least 1 of the 4 analyzed genes, whereas all urine samples from normal controls were negative. The sensitivity of MSP assay for detecting E-cadherin, p16, p14 and RASSF1A in tumor cells in voided urine was 35%, 35%, 33%, and 65%, respectively. Diagnostic sensitivity was 75% for combining RASSF1A and p14, and 83% for RASSF1A, p14 and E-cadherin. Urine cytology, however, detect only 13 (28%) cases of cancer or suspicious cancer. For detecting superficial and invasive bladder tumor, urine cytology revealed a sensitivity of 23% (6/26) and 35% (7/20), respectively. In contrast, MSP detected hypermethylation in the urine of 80% (37/46) bladder cancer patients. Moreover, hypermethylation analysis of E-cadherin, p14 or RASSF1A genes in urine sediment DNA detected in 85% (22/26) of superficial, 85% (11/13) of low grade, 75% (15/20) of invasive and 79% (26/33) of high grade bladder cancers. Importantly, hypermethylation was detected in the urine DNA of 90% (18/20) superficial tumors with negative or atypia cytology. CONCLUSIONS: Hypermethylation of E-cadherin, p14 or RASSF1A in urine sediment DNA is a potential biomarker for detecting superficial, low grade cancer. Besides, hypermethylation of these 3 genes is a valuable adjunct diagnostic marker to urine cytology, which can enhance the diagnostic accuracy and follow-up treatment of bladder cancer patients.	bladder
Identification of survivin, an inhibitor of apoptosis, in canine urinary bladder transitional cell carcinoma.	Survivin, an inhibitor of apoptosis, is overexpressed in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Survivin expression in canine TCC has not been defined. This study was designed to compare survivin expression between canine TCC and normal urinary bladder tissue. Reverse-transcriptase polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed on fresh-frozen and formalin-fixed tissues, respectively. All TCC tissues (n = 6) and 11/22 normal tissues assessed by PCR were positive for survivin. This difference was not significant (P = 0.06). With regard to IHC, 28/41 TCC samples were positive for nuclear survivin, whereas 0/46 normal tissues had nuclear immunoreactivity (P < 0.001). Cytoplasmic immunoreactivity did not significantly differ between TCC (7/41) and normal tissues (17/46) (P = 0.07). We conclude that nuclear survivin is present in canine TCC, but not in normal bladder urothelium. Future studies will evaluate the role of nuclear survivin in TCC development and as a potential therapeutic target.	bladder
Urinary tract infections and reduced risk of bladder cancer in Los Angeles.	We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.	bladder
Study of 5-Aza-CdR on transcription regulation of RASSF1A gene in the BIU87 cell line.	OBJECTIVES: To investigate the effect of 5-Aza-CdR on methylation and expression of RASSF1A gene in the human bladder cancer BIU87 cell line. METHODS: Cultured BIU87 cells were treated with increasing concentrations (0.1, 0.5, 1.0, 5.0 micromol/l) of 5-Aza-CdR. MTT was used to detect the proliferation of BIU87 cells. The methylation status and expression level of RASSF1A gene in BIU87 cells were analyzed by methylation-specific polymerase chain reaction and RT-PCR before and after treatment with 5-Aza-CdR. Meanwhile, Western blot was used to detect the changes of RASSF1A protein. RESULTS: In this study we found that the growth velocity of the BIU87 cell line was suppressed to various degrees after having been treated with different concentrations of 5-Aza-CdR, and the survival rate decreased with increasing 5- Aza-CdR concentrations. Besides, the methylation status of RASSF1A was obviously reversed and mRNA was re-expressed after treatment with 5-Aza-CdR. Expression of RASSF1A protein increased with increasing 5-Aza-CdR concentrations. CONCLUSIONS: Our results suggest that the tumor-suppressive effect of 5-Aza-CdR may result from reactivation of silenced RASSF1A through a demethylation function.	bladder
Transrectal ultrasound as diagnostic tool for the detection of local recurrence following cystectomy and urinary diversion.	OBJECTIVE: Routine follow-up after cystectomy for bladder cancer detect patients with local recurrence late in the course of disease. We set out to determine the value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local failure. PATIENTS AND METHODS: Between 1986 and 2003, radical cystectomy for bladder cancer with orthotopic diversion was performed in 642 male patients. We identified all patients that simultaneously had transabdominal ultrasound, digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of local recurrence. RESULTS: Mean follow-up was 59.4 months. 83/642 patients (13%) had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%) the local recurrence was the first site of recurrence. 35/642 patients (5.5%) developed local failure with concomitant distant disease. 31/83 patients met the inclusion criteria. The median time between cystectomy and diagnosis of local recurrence was 13 months (2-51 months). Routine follow-up detected local recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in the lower extremities/pelvis, hematuria and urinary retention, respectively. Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients, respectively. CONCLUSIONS: TRUS is a highly sensitive tool in detecting local recurrence following cystectomy. It is easy to perform and inexpensive. We recommend TRUS in short intervals in all patients with high risk for local recurrence in order to detect cancer early.	bladder
[Extending the limits of lymphadenectomy during radical cystectomy: pitfalls in the interpretation of contemporary study results].	The optimal extent of lymphadenectomy performed during radical cystectomy for transitional cell carcinoma of the bladder is currently under intensive debate. Extending the limits of lymphadenectomy has been hypothesized to add further diagnostic and therapeutic benefit. However, our current knowledge is based exclusively on results from retrospective studies that are hampered by several statistical shortcomings. This article provides a critical analysis of the contemporary data on the subject and outlines typical statistical pitfalls that must be considered when interpreting such research results.	bladder
Nuclear matrix protein 22 as adjunct to urine cytology and cystoscopy in follow-up of superficial TCC of urinary bladder.	OBJECTIVES: To assess the efficacy of nuclear matrix protein 22 (NMP-22) in the diagnosis of recurrent, superficial bladder cancer and whether it can predict for future recurrence. METHODS: Patients with diagnosed and treated superficial transitional cell carcinoma urinary bladder (Stage Ta, T1, Tis, Nx, and M0) presenting for surveillance follow-up were prospectively enrolled in this study from February 2004 to August 2005. These patients underwent urine cytology, NMP-22 testing, and cystopanendoscopy on enrollment in the study. For the next year, these patients underwent cystopanendoscopy and cytology at 3-month intervals. The ability of NMP-22 to predict for recurrence was determined using the cystoscopy findings as the reference standard. RESULTS: A total of 145 patients were included in the study. Of these, 56 had recurrence at enrollment. Of the 56 patients, 48 had positive NMP-22 findings and 22 had positive urine cytology findings. The sensitivity, specificity, positive predictive value, and negative predictive value was 85.7%, 77.5%, 70.6%, and 89.6%, respectively, for NMP-22 alone and 92.9%, 75.3%, 70.3%, and 94.4%, respectively, when the cytology and NMP-22 findings were combined. During the subsequent follow-up of 1 year, 61 recurrences developed in 47 patients. Cox regression analysis showed that those with positive NMP-22 had a 9.57 times greater risk of recurrence during 1 year compared with those with negative NMP-22. CONCLUSIONS: The results of our study have shown that the addition of NMP-22 testing to cytology increases the sensitivity for recurrence detection in patients with superficial transitional cell bladder cancer. Patients with positive NMP-22 findings developed significantly more recurrences compared with those with negative NMP-22 findings.	bladder
REG1A predicts recurrence in stage Ta/T1 bladder cancer.	AIMS: Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked tendency to recur. Regenerating protein 1 A (REG1A) has been reported to be expressed in human cancers, and it may be positively correlated with patient's prognosis. The aim of the present study was to evaluate the prognostic value of REG1A in Ta/T1 BC. METHODS: Immunohistochemistry was done on 110 paraffin-embedded specimens of human Ta/T1 BC to detect the proteins REG1A, PCNA and MMP2. The relationships between REG1A expression and the clinical-pathological characteristics of Ta/T1 BC patients were evaluated. RESULTS: Sixty-five out of 110 specimens were REG1A-positive. Grade and expression levels of MMP2 and REG1A were significantly correlated with the recurrence rate. REG1A expression (Hazard ratio: 3.1; 95% CI: 1.1-8.5; P=0.030) was an independent predictor of recurrence rate in multivariate Cox regression analysis. A significant association between REG1A expression and MMP2 expression (P=0.023) was also observed. CONCLUSION: Expression of REG1A is an independent predictor of recurrence in Ta/T1 BC.	bladder
Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.	"Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the ""carcinoma"" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers."	bladder
MicroRNA-143 as a tumor suppressor for bladder cancer.	PURPOSE: We investigated the expression and involvement of miRNA in bladder cancer. MATERIALS AND METHODS: An miRNA array was used to examine the differential expression of miRNA in tumor tissues and normal matched controls. The expression of miRNA-143 was confirmed by Northern blot and real-time polymerase chain reaction. The functional role of miRNA-143 in bladder cancer was studied by examining cell proliferation and oncogene expression after miRNA-143 transfection into 2 transitional carcinoma cell lines. RESULTS: miRNA profiling of human bladder cancer and matched normal urothelial epithelium controls revealed that 37 miRNAs were up-regulated and 38 were down-regulated in cancer tissues, of which the expression of miRNA-143 was 13.7 times lower in tumor than in the matched control. Consistent with microarray data, Northern blot analysis and real-time polymerase chain reaction confirmed that miRNA-143 expression was significantly down-regulated in bladder tumor tissues compared with normal adjacent tissues. The expression of miRNA-143 was not detected in the 2 human bladder cancer cell lines EJ and T24. Interestingly miRNA-143 transfection into EJ and T24 cells significantly inhibited cell proliferation. RAS protein expression in cancer tissues was much higher than in adjacent controls. Consistently RAS protein expression was also significantly decreased in miRNA-143 transfected cells compared with nonspecific miRNA transfected cells. CONCLUSIONS: miRNAs are differentially expressed in bladder cancer tissues. miRNA-143 may function as a tumor suppressor in bladder transitional cell carcinoma.	bladder
The development of multiple bladder tumour recurrences in relation to the FGFR3 mutation status of the primary tumour.	Non-muscle invasive bladder cancers (NMI-BCs) represent 75% of bladder cancers upon presentation. After removal of the primary tumour by transurethral resection, multiple recurrences continue to develop in 70% of patients. Consequently, prolonged and costly surveillance by cystoscopy is required. Mutations in the FGFR3 oncogene are common in NMI-BCs and are associated with a lower chance of progression to muscle-invasive disease. Here we analysed the consistency of FGFR3 mutations in primary and recurrent tumours. This knowledge is of crucial importance if FGFR3 mutation analysis on urinary cells is to be used as an alternative for cystoscopical surveillance. To this end, we monitored the disease process and FGFR3 mutation status of primary and recurrent tumours in 118 patients with NMI-BC. During median follow-up of 8.8 years, these patients underwent 2133 cystoscopies and 80 patients developed 414 recurrences. FGFR3 mutations were equally prevalent in primary and recurrent tumours (63%). Patients can have different types of FGFR3 mutations in different tumours. Recurrence risk was not significantly different for patients with a mutant or wild-type primary tumour. Recurrence rates varied widely between patients but were constant for a patient and were unrelated to FGFR3 status. In the mutant patient group, in contrast to the wild-type group, recurrences continued to develop after 10 years. In 81% of the recurrences of patients with a mutant primary tumour, a mutation was found. Moreover, recurrences in this patient group were of lower stage and grade than those of patients with a wild-type primary tumour (p < 0.001). These results suggest that surveillance by FGFR3 mutation analysis on voided urine in combination with a reduced cystoscopy frequency of patients presenting with an FGFR3 mutant tumour is worth investigating.	bladder
Favourable outcomes of patients with clinical stage T3N0M0 bladder cancer treated with induction low-dose chemo-radiotherapy plus partial or radical cystectomy vs immediate radical cystectomy: a single-institutional retrospective comparative study.	OBJECTIVES: To address the role of neoadjuvant concurrent chemo-radiotherapy (CRT) in muscle-invasive bladder cancer, by comparing retrospectively the oncological outcomes between a low-dose CRT (LCRT) plus partial cystectomy (PC) or radical cystectomy (RC) protocol and an immediate RC protocol. PATIENTS AND METHODS: From 1997 to 2007, 119 patients with clinical stage T2-4aN0M0 bladder cancer received LCRT consisting of RT of 40 Gy in 4 weeks concurrently with two cycles of chemotherapy with cisplatin (20 mg/day for 5 days) during the first and fourth week of RT. Subsequently, 24 (20%) and 65 patients (55%) had PC and RC, respectively, while 30 (25%) had no curative surgery; the median follow-up was 36 months. From 1983 to 1997, 73 patients had an immediate RC; 29 (41%) received cisplatin-based adjuvant chemotherapy, and the median follow-up was 46 months. Oncological outcomes were compared retrospectively between these groups. RESULTS: The cancer-specific survival (CSS) rate at 5 years was 75% and 61% for the LCRT protocol and immediate RC protocol, respectively (P = 0.11). In patients with clinical stage T3N0M0 the LCRT protocol gave significantly better survival rates than the immediate RC protocol, with 5-year CSS rates of 62% vs 27% (P = 0.006), while being comparable in those with clinical stage T2N0M0 disease (89% vs 88%, P = 0.84). In patients with clinical stage T3N0M0 the LCRT protocol provided a lower 5-year recurrence rate at distant sites than the immediate RC protocol (31% vs 62%, P = 0.09). CONCLUSIONS: The LCRT plus PC or RC protocol gave significantly better survival rates than the historical, immediate RC protocol in patients with clinical stage T3N0M0 bladder cancer, suggesting that neoadjuvant CRT possibly has survival benefits for such patients.	bladder
The results of concurrent chemo-radiotherapy for recurrence after treatment with bacillus Calmette-Guérin for non-muscle-invasive bladder cancer: is immediate cystectomy always necessary?	OBJECTIVES: To report our original experience in patients in whom bacille Calmette-Guérin (BCG) therapy has failed for T1 bladder cancer with subsequent progression to T2 disease treated with chemo-radiotherapy, as the management of recurrent high-grade T1 bladder cancer after failed BCG therapy is challenging, and radical cystectomy is the standard treatment because there are no well established second-line bladder-preserving therapies. PATIENTS AND METHODS: From 1988 to 2002, 18 patients with T2 recurrence after failure of BCG therapy for T1 bladder cancer were treated with chemo-radiotherapy at the authors' institution. Patients received a visibly complete transurethral resection of the bladder tumour (TURBT) and concurrent chemo-radiotherapy with a mid-treatment evaluation after 40 Gy. Patients with less than a complete response had a prompt cystectomy; the others completed radiotherapy to 64-65 Gy. The primary treatment outcome was freedom from cystectomy due to recurrence not treatable by conservative measures; secondary outcomes included disease-specific (DSS) and overall survival (OS). RESULTS: With a median follow-up of 7.0 years, only one patient had persistent tumour at re-staging TURBT and had an immediate cystectomy. Of the remaining 17 patients, 10 (59%) were free of any bladder recurrence. The actuarial 7-year DSS and OS were 70% and 58%, respectively. At 7 years, 54% of patients were alive with intact bladders and free of invasive recurrence. CONCLUSIONS: In this study we specifically evaluated patients with apparently small muscle-invasive recurrences after BCG treatment for T1 bladder cancer. Selective bladder preservation with chemo-radiotherapy is possible, with low morbidity and a high chance of long-term bladder control. If successful in treating T2 recurrences after BCG therapy, it now seems timely to critically evaluate chemo-radiotherapy as an alternative to immediate cystectomy in the management of patients with T1 recurrences after BCG.	bladder
Profiling bladder cancer organ site-specific metastasis identifies LAMC2 as a novel biomarker of hematogenous dissemination.	Little is known about which genes mediate metastasis in bladder cancer, which accounts for much of the mortality of this disease. We used human bladder cancer cell lines to develop models of two clinically common metastatic sites, lung and liver, and evaluated their gene expression with respect to human tumor tissues. Parental cells were injected into either the murine spleen to generate liver metastases or tail vein to generate lung metastases with sequential progeny derived by re-injection and comparisons made of their organ-specific nature by crossed-site injections. Both genomic and transcriptomic analyses of organ-selected cell lines found salient differences and shared core metastatic profiles, which were then screened against gene expression data from human tumors. The expression levels of laminin V gamma 2 (LAMC2) contained in the core metastatic signature were increased as a function of human tumor stage, and its genomic location was in an area of gain as measured by comparative genomic hybridization. Using immunohistochemistry in a human bladder cancer tissue microarray, LAMC2 expression levels were associated with tumor grade, but inversely with nodal status. In contrast, in node-negative patients, LAMC2 expression was associated with visceral metastatic recurrence. In summary, LAMC2 is a novel biomarker of bladder cancer metastasis that reflects the propensity of cells to metastasize via either lymphatic or hematogenous routes.	bladder